CN102309460B - Pyridostigmine bromide odor masking orally disintegrating tablets and preparation method thereof - Google Patents
Pyridostigmine bromide odor masking orally disintegrating tablets and preparation method thereof Download PDFInfo
- Publication number
- CN102309460B CN102309460B CN 201010221690 CN201010221690A CN102309460B CN 102309460 B CN102309460 B CN 102309460B CN 201010221690 CN201010221690 CN 201010221690 CN 201010221690 A CN201010221690 A CN 201010221690A CN 102309460 B CN102309460 B CN 102309460B
- Authority
- CN
- China
- Prior art keywords
- pyridostigmine bromide
- taste masking
- parts
- solid dispersion
- pyridostigmine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- VNYBTNPBYXSMOO-UHFFFAOYSA-M Pyridostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=C[N+](C)=C1 VNYBTNPBYXSMOO-UHFFFAOYSA-M 0.000 title claims abstract description 68
- 229960002151 pyridostigmine bromide Drugs 0.000 title claims abstract description 68
- 238000002360 preparation method Methods 0.000 title claims abstract description 32
- 230000000873 masking effect Effects 0.000 title claims abstract description 31
- 239000006191 orally-disintegrating tablet Substances 0.000 title abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 21
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000000945 filler Substances 0.000 claims abstract description 12
- 239000000796 flavoring agent Substances 0.000 claims abstract description 4
- 235000019640 taste Nutrition 0.000 claims description 27
- 239000007962 solid dispersion Substances 0.000 claims description 21
- 239000003814 drug Substances 0.000 claims description 20
- 238000002156 mixing Methods 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 12
- 229930195725 Mannitol Natural products 0.000 claims description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 12
- 239000000594 mannitol Substances 0.000 claims description 12
- 235000010355 mannitol Nutrition 0.000 claims description 12
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 10
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 10
- 239000008101 lactose Substances 0.000 claims description 10
- 239000000314 lubricant Substances 0.000 claims description 10
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 10
- 239000004376 Sucralose Substances 0.000 claims description 9
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 9
- 235000019408 sucralose Nutrition 0.000 claims description 9
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 claims description 9
- 235000010357 aspartame Nutrition 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 238000009702 powder compression Methods 0.000 claims description 8
- 108010011485 Aspartame Proteins 0.000 claims description 7
- 239000002671 adjuvant Substances 0.000 claims description 7
- 239000000605 aspartame Substances 0.000 claims description 7
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 7
- 229960003438 aspartame Drugs 0.000 claims description 7
- 239000012153 distilled water Substances 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 239000007779 soft material Substances 0.000 claims description 7
- 239000012467 final product Substances 0.000 claims description 6
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 5
- 235000006679 Mentha X verticillata Nutrition 0.000 claims description 5
- 235000002899 Mentha suaveolens Nutrition 0.000 claims description 5
- 235000001636 Mentha x rotundifolia Nutrition 0.000 claims description 5
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 235000010356 sorbitol Nutrition 0.000 claims description 5
- 239000004925 Acrylic resin Substances 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 3
- 229920000178 Acrylic resin Polymers 0.000 claims description 3
- 229960004998 acesulfame potassium Drugs 0.000 claims description 3
- 239000000619 acesulfame-K Substances 0.000 claims description 3
- 235000009508 confectionery Nutrition 0.000 claims description 3
- 238000004132 cross linking Methods 0.000 claims description 3
- 235000019634 flavors Nutrition 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 3
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 2
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 claims description 2
- QGGZBXOADPVUPN-UHFFFAOYSA-N dihydrochalcone Chemical compound C=1C=CC=CC=1C(=O)CCC1=CC=CC=C1 QGGZBXOADPVUPN-UHFFFAOYSA-N 0.000 claims description 2
- PXLWOFBAEVGBOA-UHFFFAOYSA-N dihydrochalcone Natural products OC1C(O)C(O)C(CO)OC1C1=C(O)C=CC(C(=O)CC(O)C=2C=CC(O)=CC=2)=C1O PXLWOFBAEVGBOA-UHFFFAOYSA-N 0.000 claims description 2
- 238000007907 direct compression Methods 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 claims description 2
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 claims description 2
- 229940025878 hesperidin Drugs 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims description 2
- 238000005498 polishing Methods 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 238000001694 spray drying Methods 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 238000005469 granulation Methods 0.000 claims 2
- 230000003179 granulation Effects 0.000 claims 2
- 239000003826 tablet Substances 0.000 abstract description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 abstract description 4
- 238000005550 wet granulation Methods 0.000 abstract description 4
- 208000019505 Deglutition disease Diseases 0.000 abstract description 3
- 230000001186 cumulative effect Effects 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 235000013355 food flavoring agent Nutrition 0.000 abstract 1
- 210000000214 mouth Anatomy 0.000 description 33
- 238000012360 testing method Methods 0.000 description 10
- -1 mixing sieves Substances 0.000 description 9
- 239000000686 essence Substances 0.000 description 8
- 235000019658 bitter taste Nutrition 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229960002290 pyridostigmine Drugs 0.000 description 7
- 238000012216 screening Methods 0.000 description 7
- 229920003119 EUDRAGIT E PO Polymers 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 206010013786 Dry skin Diseases 0.000 description 5
- 229920003149 Eudragit® E 100 Polymers 0.000 description 5
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 230000006837 decompression Effects 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 4
- 239000007968 orange flavor Substances 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 3
- 229960004373 acetylcholine Drugs 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 206010028417 myasthenia gravis Diseases 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- 102000009660 Cholinergic Receptors Human genes 0.000 description 2
- 108010009685 Cholinergic Receptors Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000005496 eutectics Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000009747 swallowing Effects 0.000 description 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 1
- QUXMXCWHPRNHQS-UHFFFAOYSA-N CN1CC(CC=C1)=O Chemical compound CN1CC(CC=C1)=O QUXMXCWHPRNHQS-UHFFFAOYSA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 229940122041 Cholinesterase inhibitor Drugs 0.000 description 1
- YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 description 1
- YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 description 1
- 206010056474 Erythrosis Diseases 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 206010022086 Injection site pain Diseases 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- WXOMTJVVIMOXJL-BOBFKVMVSA-A O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)OS(=O)(=O)OC[C@H]1O[C@@H](O[C@]2(COS(=O)(=O)O[Al](O)O)O[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]2OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]1OS(=O)(=O)O[Al](O)O Chemical compound O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)O.O[Al](O)OS(=O)(=O)OC[C@H]1O[C@@H](O[C@]2(COS(=O)(=O)O[Al](O)O)O[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]2OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@@H]1OS(=O)(=O)O[Al](O)O WXOMTJVVIMOXJL-BOBFKVMVSA-A 0.000 description 1
- 240000007711 Peperomia pellucida Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 206010016766 flatulence Diseases 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 235000015250 liver sausages Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000001611 motor endplate Anatomy 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 230000003551 muscarinic effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- DWLVWMUCHSLGSU-UHFFFAOYSA-M n,n-dimethylcarbamate Chemical compound CN(C)C([O-])=O DWLVWMUCHSLGSU-UHFFFAOYSA-M 0.000 description 1
- 229960002362 neostigmine Drugs 0.000 description 1
- LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229960002715 nicotine Drugs 0.000 description 1
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000003507 refrigerant Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to pyridostigmine bromide odor masking orally disintegrating tablets and a preparation method thereof. The tablets belong to orally disintegrating tablets, and the orally disintegrating tablets consist of pyridostigmine bromide, an odor masking agent, a filling agent, a disintegrating agent and a flavoring agent basically, can be prepared by a direct tablet compressing process or a wet granulation process, have good mouthfeel and are disintegrated for 20 to 45 seconds; and in the dissolution detection process, the average cumulative dissolution quantity in 0.1mol/L of hydrochloric acid medium within 5 minutes is more than 85 percent. The tablets have good mouthfeel and quick response, are quickly disintegrated and convenient to take, and are particularly suitable to be taken by the old, children and patients who suffer from dysphagia and are in special environments (such as an environment in which water is difficult to take). The preparation method does not have special requirements on equipment, and products have controllable quality and low cost, and are easy to produce industrially.
Description
Technical field
The present invention relates to a kind of new formulation of myasthenia gravis medicine pyridostigmine bromide, be specifically related to a kind of pyridostigmine bromide taste masking orally disintegrating tablet preparation with rapid release effect, good mouthfeel and preparation method thereof.
Background technology
Pyridostigmine bromide (Pyridostigmine Bromide, pyridostigmine bromide) this product is cholinesterase inhibitor, chemical name: 1-methyl-3-pyridone dimethyl carbamate, molecular formula: C
9H
13BrN
2O
2, molecular weight: 261.12.Pyridostigmine bromide can reversiblely be combined with acetylcholine esterase, endogenous acetylcholine is piled up in vivo, muscarinic and the excitation of nicotine sample choline cholinoceptor appear, in addition, nicotinic cholinergic receptor on the motor end plate there is direct excitation, and can promote motor nerve ending to discharge acetylcholine, excited smooth muscle, striped muscle are arranged and suppress cardiovascular effect, a little less than the effect than neostigmine, but more lasting, be mainly used in treating myasthenia gravis, also can be used for treatment operation venter posterior flatulence and urine retention.At present, the pyridostigmine bromide common formulations has injection, syrup and three kinds of preparations of coated tablet clinically.Specification: injection: 1mg/1ml, 5mg/1ml; Syrup: 12mg/1ml; Tablet: 60mg.Usage and consumption: myasthenia gravis, the adult: oral 60～120mg/ time, 3～4 times on the 1st.Be used for other treatment and be advisable with intramuscular injection, the 1mg onset is once measured with 4～6mg and is limited, and maximum dose is 0.6mg/kg per hour.
All there are some defectives in existing pyridostigmine bromide dosage form: injection inconvenience prolonged application with and produce pain during injection, reduced patient's compliance; Syrup transports and carries inconvenience; Sugar coated tablet then disintegrate is slow, and drug-eluting is slow, needs drinking-water and finishes drug administration process by swallowing act, give old man, child and have dysphagia patients to bring inconvenience, and diabetics is taken syrup and also there is potential risk in coated tablet.The exploitation good mouthfeel, disintegrate is rapid, rapid-action, carries, taking convenience, and the pyridostigmine bromide oral cavity disintegration tablet that can improve patient's compliance has important value for clinical application.
Oral cavity disintegration tablet is a kind of new medicinal preparation form, means that a kind of not need water (or a small amount of water) in the oral cavity be the tablet of disintegrate or dissolving.Oral cavity disintegration tablet has following advantage: this dosage form in the oral cavity fast disintegrate, good mouthfeel, easily swallow, non-stimulated to oral mucosa; This dosage form is rapid-action, can bring into play rapidly curative effect of medication; This dosage form need not water, can normally take under anhydrous condition, thereby convenient patient uses in the hydropenia situation such as go out; This dosage form only needs to finish drug administration process by very little swallowing act, is fit to old man, child or has the patient of dysphagia to take; This dosage form avoids liver sausage first pass effect, bioavailability high.
Therefore, be necessary to develop the pyridostigmine bromide oral cavity disintegration tablet, for clinical application provides more selection, satisfy the clinical application demand, bring into play better the pyridostigmine bromide curative effect, make drug use convenient, improve patient's medication compliance.The pyridostigmine bromide orally disintegrating tablet preparation has wide market application foreground.
But the pyridostigmine bromide bitter in the mouth is prepared into oral cavity disintegration tablet with it, need to solve sensory issues, and it is one of exploitation pyridostigmine bromide oral cavity disintegration tablet key technology that principal agent is carried out that taste masking and taste masking process.
Summary of the invention
The invention provides a kind of drug-eluting rapidly, the preparation method of the novel pyridostigmine bromide orally disintegrating tablet preparation of good mouthfeel, and provide pyridostigmine bromide carried out method and the technology that taste masking and taste masking are processed.
Technical solution of the present invention is as follows:
The invention provides a kind of serious symptom muscle weakness medicine pyridostigmine bromide orally disintegrating tablet preparation, with pyridostigmine bromide as principal agent, comprised the adjuvant on pyridostigmine bromide taste masking solid dispersion and the pharmaceutics, it is characterized in that: it is the solid dispersion that is prepared from take odor mask as carrier that described pyridostigmine bromide taste masking is processed; Acceptable adjuvant is water-soluble filler, disintegrating agent, correctives and lubricant on the described pharmaceutics.
The weight ratio that the present invention comprises consists of:
10 parts～40 parts of pyridostigmine bromide taste masking solid dispersion
20 parts～50 parts of water-soluble fillers
4 parts～20 parts of disintegrating agents
0.5 part～3.0 parts of correctivess
1 part～5 parts of lubricants
Pyridostigmine bromide of the present invention is processed through taste masking first, and odor mask is acrylic resin IV class (stomach dissolution type macromolecular material), and the odor mask consumption is in weight ratio, pyridostigmine bromide: odor mask=1: 1～4.
Taste masking of the present invention is processed and is adopted solid dispersions technique to comprise polishing, solvent evaporated method, spray drying method and freeze-drying.
When among the present invention medicine being carried out taste masking and process, need to add correctives and cover remaining bitterness, correctives is selected from one or more in aspartame, acesulfame potassium, sucralose, Hesperidin dihydrochalcone, the sweet peptide factor, fruity flavor or the Mint Essence.
Water-soluble filler of the present invention is one or more in lactose, sugar alcohols (mannitol, sorbitol, xylitol and erythrose) preferably; Disintegrating agent preferably two kinds in microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, crospolyvinylpyrrolidone and more than; One or more of the optional magnesium stearate of lubricant, micropowder silica gel, Pulvis Talci, Polyethylene Glycol apoplexy due to endogenous wind.
Oral cavity disintegration tablet of the present invention can prepare with direct powder compression or wet granulation technology.Reduce cost, equipment requirements is low, can realize suitability for industrialized production.(1) adopt direct powder compression to prepare the pyridostigmine bromide oral cavity disintegration tablet, the pyridostigmine bromide solid dispersion adds one or more in the filler, in the disintegrating agent two kinds and more than, in the correctives one or more and the lubricant mixing that sieves, direct compression and get final product.(2) adopt wet granulation technology to prepare the pyridostigmine bromide oral cavity disintegration tablet, the pyridostigmine bromide solid dispersion adds a kind of or several in the filler, in the disintegrating agent two kinds and more than, mixing sieves, distilled water soft material processed, 16～24 mesh sieves are granulated, 40～50 ℃ of dryings 0.5～2 hour, 16～24 mesh sieve granulate, add lubricant, mix homogeneously, tabletting and get final product.(3) adopt wet granulation technology to prepare the pyridostigmine bromide oral cavity disintegration tablet, the pyridostigmine bromide solid dispersion adds a kind of or several in the filler, two kinds and an above part in the disintegrating agent, mixing sieves, distilled water soft material processed, 16～24 mesh sieves are granulated, 40～50 ℃ of dryings 0.5～2 hour, 16～24 mesh sieve granulate, add the another part in lubricant and the disintegrating agent, mix homogeneously, tabletting and get final product.
The present invention adopts mouthfeel assessment method screening solid dispersion optimal drug and odor mask ratio: select 5 volunteers, get respectively solid dispersion an amount of (approximately containing medicine 20mg), put into the oral cavity; but normal activity during the pastille; but must not drink water, spue behind the 30s, the impression of immediate record buccal.Each sample inspection intervals 30min.When pyridostigmine bromide and odor mask ratio reach 1: 3 and be above, can cover the pyridostigmine bromide bitterness.The present invention has adopted the group characteristic absorption of infrared spectroscopy, has adopted simultaneously the fusing suction exothermic characteristic of melting point determination and differential scanning calorimetry to verify solid dispersion, and this several method has all been verified solid dispersion formation.It is 98.75% that the taste masking solid dispersion prepares yield.
The present invention has adopted the evaluation of many indexs that the pyridostigmine bromide orally disintegrating tablet preparation is carried out quality control: outward appearance and mouthfeel comprehensive grading, weight differential inspection, hardness test, disintegration, assay and dissolution in vitro test.
The comprehensive grading results such as table 1 pyridostigmine bromide oral cavity disintegration tablet outward appearance and mouthfeel
Comprehensive grading=outward appearance scoring+refrigerant sense scoring+dry sensation scoring+bitterness scoring
Carry out pharmacokinetics research in the body with pyridostigmine bromide orally disintegrating tablet preparation provided by the invention.Select 12 of healthy new zealand white rabbit, be divided into 2 groups, i.e. pyridostigmine bromide orally disintegrating tablet preparation group; Listing pyridostigmine bromide coated tablet group, 6 every group, the single dose trial design.The front fasting 12h that takes medicine, after the administration 0.25,0.5,1.0,1.5,2,2.5,3,4,5,6,8,10,12,24h is in rabbit ear edge venous blood sampling, and the centrifugal 10min of 3000rmp separates obtaining plasma sample, puts-80 ℃ of Refrigerator stores, and is to be measured.The intersection administration is got hematometry blood drug level with different time after two groups of administrations after 1 week, with DAS2.0 pharmacokinetics software data processing, and carries out statistical analysis.Adopt RPIC to measure the rabbit vivo medicine concentration, the method accurately and reliably, favorable reproducibility.At 0.02～2 μ g.mL
-1In the scope, drug level and peak area linear relationship are good, and in a few days, day to day precision is less than 2%, absolute recovery is 85.55% ± 8.7%, and relative recovery is 95.42% ± 1.92%.Pharmacokinetic in the rabbit body shows, it is 1 one-compartment model that pyridostigmine bromide oral cavity disintegration tablet and commercially available coated tablet pharmacokinetics all meet weight.The former Cmax is 1782ngmL
-1Be lower than commercially available prod (pyridostigmine bromide coated tablet), t1/2 is 3.136h, shorter than commercially available prod (t1/2 is 3.437h), AUC0-24 is that 1568.1ng.mL-1.h, AUC0-∝ are 1584.1ng.mL-1.h, all than commercially available prod (AUC0-24 is that 1470.1ng.mL-1.h, AUC0-∝ are 1527.7ng.mL-1.h) height, studies show that the M11 oral cavity disintegration tablet absorbs rapidly, the sustainable medicine that discharges more reposefully, bioavailability is higher.
Studies show that the comparatively fast onset of pyridostigmine bromide oral cavity disintegration tablet, bioavailability is high.
Advantage of the present invention is: pyridostigmine bromide is water soluble drug, bitter in the mouth, directly add correctives and can not shelter bitterness fully, mouthfeel is poor, add polyacrylic resin IV class and be prepared into taste masking solid dispersion powder, make medicine not stripping in the oral cavity, Fast Stripping in the gastric juice, the dispersibility of medicine can be improved when improving the medicine mouthfeel, the rendezvous problem of pyridostigmine bromide micronized particles can be avoided adopting merely; Select the rapidly dissolvings in mouth such as water-soluble filler mannitol, cool taste is little sweet, and disintegrate is affected almost without impact; Preferred two kinds and above good disintegrating agent produce synergism, shorten disintegration time; The adding of the correctives such as aspartame, fruity flavor, the remaining bitterness of energy masking agents improves mouthfeel.Oral cavity disintegration tablet good mouthfeel, the disintegrate of making is rapid, stripping is fast, taking convenience, improves patient's compliance.And preparation technology is simple and easy to control for this oral cavity disintegration tablet, is fit to very much industrialized great production.
The specific embodiment
Embodiment 1
The weight ratio of components of each component that contains in the prescription is:
7.5 parts of pyridostigmine bromides
7.5 parts of Eudragit E100
50 parts in mannitol
15 parts of microcrystalline Cellulose
5 parts of crospolyvinylpyrrolidone
2.5 parts of aspartames
5 parts of magnesium stearate
Preparation method:
Pyridostigmine bromide is crossed 80 mesh sieves, is added among the Eudragit E100 of melting mixing, the cooling eutectic is pulverized rapidly, screening 80～100 order powder, add other adjuvants such as mannitol, mix homogeneously, direct powder compression get sheet and heavily are 1000 of the oral cavity disintegration tablets of 200mg.
Result of the test:
Embodiment 2
The weight ratio of components of each component that contains in the prescription is:
7.5 parts of pyridostigmine bromides
30 parts of Eudragit E100
17.5 parts of lactose
20 parts of sorbitol
15 parts of carboxymethyl starch sodium
5 parts of low-substituted hydroxypropyl celluloses
1.5 parts of acesulfame potassiums
1.5 parts of Mint Essences
2 parts of Pulvis Talci
Preparation method:
Pyridostigmine bromide is crossed 80 mesh sieves, is added among the Eudragit E100 of melting mixing, the cooling eutectic is pulverized rapidly, screening 80～100 order powder, add the adjuvants (except Pulvis Talci and the Mint Essence) such as lactose, mixing, distilled water soft material processed, 24 mesh sieves are granulated, 40 ℃ of dryings, 20 mesh sieve granulate add Mint Essence and Pulvis Talci, and the mixing tabletting gets sheet and heavily is 1000 of the oral cavity disintegration tablets of 200mg.
Result of the test:
Embodiment 3
The weight ratio of components of each component that contains in the prescription is:
15 parts of pyridostigmine bromides
25 parts of Eudragit E100
30 parts of lactose
10 parts in mannitol
8 parts of carboxymethyl starch sodium
12 parts of cross-linking sodium carboxymethyl celluloses
1.6 parts of sucralose
2.4 parts of magnesium stearate
Preparation method:
Get Eudragit E100,90 parts of dissolve with ethanol solutions add the pyridostigmine bromide mix homogeneously, volatilize most of solvent, vacuum decompression is dry, pulverizes screening 80～100 order powder, add the adjuvants such as lactose, mix homogeneously, direct powder compression get sheet and heavily are 1000 of the oral cavity disintegration tablets of 250mg.
Result of the test:
Embodiment 4
The weight ratio of components of each component that contains in the prescription is:
3.5 parts of pyridostigmine bromides
10.5 parts of Eudragit EPO
25 parts in mannitol
12 parts of microcrystalline Cellulose
6 parts of low-substituted hydroxypropyl celluloses
0.5 part of aspartame
1 part in orange flavor essence
1 part of micropowder silica gel
Preparation method:
Get Eudragit EPO, 90 parts of dissolve with ethanol solutions, the dissolving of adding pyridostigmine bromide also is uniformly dispersed, volatilize most of solvent, vacuum decompression is dry, pulverize, screening 80～100 order powder add mannitol, a part of microcrystalline Cellulose and low-substituted hydroxypropyl cellulose, aspartame and orange flavor essence, mixing, distilled water soft material processed, 24 mesh sieves are granulated, 40 ℃ of dryings, 20 mesh sieve granulate, add micropowder silica gel and remaining part microcrystalline Cellulose and low-substituted hydroxypropyl cellulose, the mixing tabletting gets sheet and heavily is 1000 of the oral cavity disintegration tablets of 250mg.
Result of the test:
Embodiment 5
The weight ratio of components of each component that contains in the prescription is:
15 parts of pyridostigmine bromides
20 parts of Eudragit EPO
30 parts in mannitol
20 parts of lactose
16 parts of low-substituted hydroxypropyl celluloses
4 parts of crospolyvinylpyrrolidone
2 parts of sucralose
2.5 parts of Pulvis Talci
Preparation method:
Get Eudragit EPO, anhydrous alcohol solution, the dissolving of adding pyridostigmine bromide also is uniformly dispersed, volatilize most of solvent, vacuum decompression is dry, pulverizes screening 80～100 order powder, add lactose, mannitol, crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, sucralose and Pulvis Talci, mix homogeneously direct powder compression sheet heavily is 1000 of the oral cavity disintegration tablets of 300mg.
Result of the test:
Embodiment 6
The weight ratio of components of each component that contains in the prescription is:
15 parts of pyridostigmine bromides
25 parts of Eudragit EPO
40 parts of sorbitol
5 parts of microcrystalline Cellulose
10 parts of crospolyvinylpyrrolidone
1.5 parts of acesulfame potassiums
1.5 parts of sucralose
3 parts of magnesium stearate
Preparation method:
Get Eudragit EPO, anhydrous alcohol solution, the dissolving of adding pyridostigmine bromide also is uniformly dispersed, volatilize most of solvent, vacuum decompression is dry, pulverizes, screening 80～100 order powder add sorbitol, microcrystalline Cellulose, crospolyvinylpyrrolidone, acesulfame potassium and sucralose, mix homogeneously, distilled water soft material processed, 24 mesh sieves are granulated, 40 ℃ of dryings, 20 mesh sieve granulate, add magnesium stearate, the mixing tabletting gets sheet and heavily is 1000 of the oral cavity disintegration tablets of 300mg.
Result of the test:
Embodiment 7 (control experiment: directly the taste masking legal system is for oral cavity disintegration tablet)
The weight ratio of components of each component that contains in the prescription is:
10 parts of pyridostigmine bromides
20 parts of lactose
30 parts in mannitol
10 parts of microcrystalline Cellulose
6 parts of low-substituted hydroxypropyl celluloses
4 parts of crospolyvinylpyrrolidone
1 part of aspartame
1.3 parts of sucralose
0.7 part in orange flavor essence
1.6 parts of Pulvis Talci
Preparation method:
Get pyridostigmine bromide, mannitol, lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, crospolyvinylpyrrolidone, sucralose, aspartame, orange flavor essence and Pulvis Talci, cross 100 mesh sieve micronizations, mix homogeneously, direct powder compression get sheet and heavily are 1000 of the oral cavity disintegration tablets of 300mg.
Result of the test:
Above test explanation, directly the taste masking method can not be covered medicine pyridostigmine bromide bitterness, and masking agents bitterness in various degree after processing through odor mask, affect hardly disintegration, all prescription disintegrations all qualified (in 1 minute), 5 minutes accumulation stripping quantities are greater than 85% in the dissolution test 0.1mol/L hydrochloric acid medium, and commercially available coated tablet accumulation stripping quantity is less than 10%, the pyridostigmine bromide Novel mouth disintegrating preparations good mouthfeel of development, can reach rapidly disintegrate after the administration, discharge the requirement of medicine.
Claims (6)
1. pyridostigmine bromide taste masking oral rapidly disintegrating tablet preparation is characterized in that this tablet is to be made by pyridostigmine bromide taste masking solid dispersion and other adjuvant by following weight ratio:
Pyridostigmine bromide taste masking solid dispersion comprises following component, and its weight consists of:
1 part of pyridostigmine bromide
1～4 part of acrylic resin IV
It is that pyridostigmine bromide is prepared into solid dispersion take acrylic resin IV as disperse medium that taste masking is processed.
2. pyridostigmine bromide taste masking oral rapidly disintegrating tablet preparation according to claim 1, the filler in the component is one or more in lactose, mannitol, sorbitol, the xylitol.
3. pyridostigmine bromide taste masking oral rapidly disintegrating tablet preparation according to claim 1, the disintegrating agent in the component be in microcrystalline Cellulose, carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, the crospolyvinylpyrrolidone two kinds and more than.
4. pyridostigmine bromide taste masking oral rapidly disintegrating tablet preparation according to claim 1, the correctives in the component is one or more in aspartame, acesulfame potassium, sucralose, Hesperidin dihydrochalcone, the sweet peptide factor, fruity flavor or the Mint Essence.
5. pyridostigmine bromide taste masking oral rapidly disintegrating tablet preparation according to claim 1, the lubricant in the component is one or more in magnesium stearate, micropowder silica gel, the Pulvis Talci.
6. the preparation method of pyridostigmine bromide taste masking oral rapidly disintegrating tablet preparation according to claim 1, it is characterized in that the method may further comprise the steps: (1) solid dispersions technique prepares pyridostigmine bromide taste masking solid dispersion, and preparation method is selected from polishing, solvent evaporated method, spray drying method and freeze-drying; (2) tabletting: tabletting behind direct powder compression or the drug moiety adjuvant mixing granulation, the A method is direct powder compression: with pyridostigmine bromide solid dispersion, water-soluble filler, disintegrating agent, correctives and mix lubricant, direct compression and get final product; The B method is with the pyridostigmine bromide solid dispersion, adds water-soluble filler, disintegrating agent and correctives, the mixing that sieves, and distilled water soft material processed, 16～24 mesh sieves are granulated, the granulate that sieves after the drying, adding lubricant, mix homogeneously, tabletting and get final product; The C method is that the pyridostigmine bromide solid dispersion is added a part in filler, the disintegrating agent and the correctives mixing that sieves, distilled water soft material processed, the granulation of 16～24 mesh sieves, granulate sieves after the drying, add another part disintegrating agent and lubricant, mix homogeneously, tabletting and get final product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010221690 CN102309460B (en) | 2010-07-09 | 2010-07-09 | Pyridostigmine bromide odor masking orally disintegrating tablets and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010221690 CN102309460B (en) | 2010-07-09 | 2010-07-09 | Pyridostigmine bromide odor masking orally disintegrating tablets and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102309460A CN102309460A (en) | 2012-01-11 |
| CN102309460B true CN102309460B (en) | 2013-04-24 |
Family
ID=45423283
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010221690 Expired - Fee Related CN102309460B (en) | 2010-07-09 | 2010-07-09 | Pyridostigmine bromide odor masking orally disintegrating tablets and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102309460B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013136346A2 (en) * | 2012-03-15 | 2013-09-19 | Katakam Venkatesh | Taste masking pharmaceutical orally dissolving strips of lornoxicam |
| CN103330942A (en) * | 2013-06-19 | 2013-10-02 | 山东鲁抗舍里乐药业有限公司 | Florfenicol smell masking preparation and preparation method thereof |
| CN113288872A (en) * | 2020-02-21 | 2021-08-24 | 广东东阳光药业有限公司 | Composition of 2-pyrrolidone derivative and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1523980A (en) * | 2000-12-07 | 2004-08-25 | ��̹��ҽҩ��˾ | Pharmaceutical preparation comprising an active dispersed on a matrix |
| CN101166543A (en) * | 2005-04-28 | 2008-04-23 | 卫材R&D管理有限公司 | Composition containing antidementia agent |
-
2010
- 2010-07-09 CN CN 201010221690 patent/CN102309460B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1523980A (en) * | 2000-12-07 | 2004-08-25 | ��̹��ҽҩ��˾ | Pharmaceutical preparation comprising an active dispersed on a matrix |
| CN101166543A (en) * | 2005-04-28 | 2008-04-23 | 卫材R&D管理有限公司 | Composition containing antidementia agent |
Non-Patent Citations (6)
| Title |
|---|
| 何燕等.国内外口服制剂掩味技术的研究进展.《中国新药杂志》.2010,第19卷(第8期),第671-675页. |
| 固体分散载体材料在药物制剂中的应用概况;孙耀贵等;《中兽医医药杂志》;20100410(第2期);第28-32页 * |
| 国内外口服制剂掩味技术的研究进展;何燕等;《中国新药杂志》;20100430;第19卷(第8期);第671-675页 * |
| 孙耀贵等.固体分散载体材料在药物制剂中的应用概况.《中兽医医药杂志》.2010,(第2期),第28-32页. |
| 张梨等.溴吡斯的明-β-环糊精包合物的研制.《中国医院药学杂志》.2010,第30卷(第6期),第466-470页. |
| 溴吡斯的明-β-环糊精包合物的研制;张梨等;《中国医院药学杂志》;20100330;第30卷(第6期);第466-470页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102309460A (en) | 2012-01-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8647668B2 (en) | Tablet quickly disintegrating in oral cavity | |
| US20220039455A1 (en) | Pouched product with liquid flavor composition | |
| TWI376243B (en) | Oral disintegrating tablet | |
| US20090311321A1 (en) | Oral disintegrating tablet having masked bitter taste and method for production thereof | |
| WO2000078292A1 (en) | Quickly disintegrating solid preparations | |
| WO1999018936A1 (en) | Quickly soluble solid preparations | |
| JP6392207B2 (en) | Orally administered formulation masking the bitter taste of silodosin | |
| WO2012121461A1 (en) | Stable fast-dissolving film formulation for oral dosage form | |
| JP2001058944A (en) | Rapidly disintegrating solid formulation | |
| CN103813785A (en) | New abuse-resistant pharmaceutical composition for the treatment of opioid dependence | |
| WO2007086457A1 (en) | Quickly disintegrating tablet produced by direct dry-tabletting | |
| CN100588400C (en) | Fast disintegrant containing paroxetine | |
| CN105030735A (en) | Memantine hydrochloride oral-dissolving film preparation and preparation method and application of preparation | |
| JP2013136526A (en) | Orally disintegrable tablet and method of producing the same | |
| CN107913256A (en) | A kind of macitentan oral disnitegration tablet for treating pulmonary hypertension and preparation method thereof | |
| CN102309460B (en) | Pyridostigmine bromide odor masking orally disintegrating tablets and preparation method thereof | |
| JP2705787B2 (en) | Easy to take bitterness improving H 改善 2Ｈ blocker solid preparation | |
| WO2006109737A1 (en) | Pranlukast hydrate-containing preparation having relieved bitterness | |
| TW200936184A (en) | An orally disintegrating tablet | |
| KR101302293B1 (en) | Orally disintegrating powder comprising cilostazol and mannitol | |
| JP3899522B2 (en) | Formulation containing pranlukast hydrate with reduced bitterness | |
| US20110060008A1 (en) | Pharmaceutical composition containing acetylcholine esterase inhibitor and method for the preparation thereof | |
| CN112426408A (en) | Melatonin composition and preparation process thereof | |
| CN100450470C (en) | Rapid disintegrate tablet in oral and its preparation method | |
| CN102309461B (en) | Pyridostigmine bromide odor masking dispersible tablets and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130424 |